Search

1. Large artery stiffness is a principal determinant of pulse pressure and both are related to cardiovascular mortality independently of other major risk factors. A clearer understanding of the structural and genetic processes that contribute to large artery properties may provide novel approaches to therapy. 2. Age, atherosclerosis and gender are three important factors that contribute to large artery stiffening. Each influences the artery elastic matrix and its relationship to medial smooth muscle cells. Genetic and hormonal modulation of the extracellular matrix proteins and their regulators, including matrix metalloproteinases (MMPs), may account for some interindividual differences. 3. In a study of 213 healthy individuals and 105 patients with coronary artery disease (CAD), we examined whether stromelysin-1 (MMP-3) genotype, determined by the 5A/6A promoter polymorphism, influences large artery stiffening. In healthy individuals, the 5A/5A genotype was linked with stiffer large arteries and higher systolic blood pressure compared with other genotypes. 4. Genetic variation in the extracellular matrix protein fibrillin-1, using a pentanucleotide repeat polymorphism, was assessed as a potential determinant of large artery stiffness in patients with CAD. The 2-3 genotype was associated with stiffer large arteries, higher pulse pressure and more severe CAD than other genotypes. 5. Females experience a greater increase in large artery stiffness with age than males, with a time-course suggestive of sex steroid modulation. The mechanisms mediating such gender differences have not been established, but the known regulatory role of sex steroids with respect to MMPs likely contributes. 6. The demonstration that genetic and hormonal modulation of extracellular matrix components and MMPs contributes to age, atherosclerotic and gender-related differences in large artery mechanical properties suggests these proteins may be important targets for therapy.

1. Both microalbuminuria and left ventricular hypertrophy may reflect target organ damage in essential hypertension. Both are related to the prevailing level of blood pressure and both are associated with an increase in morbidity and mortality. 2. The database of the Hypertension Diagnostic Service, a multicentre secondary referral clinic for patients with essential hypertension, was analysed in order to clarify the level of association between microalbuminuria and left ventricular hypertrophy, which might explain the observed increase in morbidity and mortality in patients with microalbuminuria. Microalbuminuria was measured semiquantitatively by urine dip-stix. After the exclusion of patients with potential secondary hypertension, renal disease and diabetes mellitus, patients with complete data for microalbuminuria, left ventricular mass (LVM) and 24 h blood pressure monitoring were selected. 3. Data were complete for 704 patients (47% male, age 51 +/- 12 years) and 42% tested positive for microalbuminuria. Microalbuminuria was positively related to 24 h systolic blood pressure and weight and was negatively related to age. Left ventricular mass was higher in patients with microalbuminuria (men, 265 +/- 69 g; women, 207 +/- 61 g) than in those without (men, 250 +/- 64 g, P < 0.05; women, 185 +/- 50 g, P < 0.001). After correction for the effects of gender, body mass index and 24 h systolic blood pressure, the presence of microalbuminuria was associated with an increase in LVM of 10 g (P < 0.05, 95% confidence interval, 2-19 g).

1. The present study was designed to compare and contrast the effects of 1 year's treatment with angiotensin-converting enzyme inhibition (captopril 25-100 mg daily) and beta-blockade (atenolol 50-100 mg daily) on hypertensive cardiac structure and function as well as the other established cardiovascular risk factors of high blood pressure (BP), lipid profile and blood glucose. 2. This was a prospective randomized open drug trial with blinded end-point echocardiographic and cardiac Doppler assessment in 37 subjects who had primary essential hypertension and left ventricular hypertrophy of captopril (n = 20) versus atenolol (n = 17), adding hydrochlorothiazide if BP was not controlled by 1 month. Multiple time point measurements throughout the 1 year treatment period of the study were made of BP, echocardiographic parameters of cardiac structure and function, as well as lipid profile and blood glucose. 3. There were no significant between-group differences for captopril or atenolol with regard to BP (at baseline (mean +/- SD) 154.0/101.1 +/- 13.3/5.1 and 152.5/101.8 +/- 10.0/5.8 mmHg, respectively) which was normalized by 1 month (138.7/85.6 +/- 18.8/11.7 and 135.4/88.5 +/- 16.9/9.5 mmHg, respectively) in both treatment groups (both P < 0.01 vs baseline). Also, there were no between-group or within-group differences for any of the measures of left ventricular hypertrophy or systolic function throughout the 12 month treatment period; however, captopril alone significantly increased left ventricular early diastolic filling (P < 0.05 vs baseline) at most of the measured time points. Furthermore, there were no significant between- or within-group differences with regard to metabolic (lipids and glucose) profile over the 1 year treatment period of the present study. 4. Markers of cardiovascular risk, including BP, echocardiographic measures of left ventricular hypertrophy, lipid profile and blood glucose were not significantly different between therapies. Despite good BP control by 1 month, neither drug regimen regressed left ventricular hypertrophy. However, captopril significantly increased left ventricular early diastolic filling after 3 months of treatment.

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was > or = 160 mmHg systolic or > or = 90 mmHg diastolic if systolic BP was > or = 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82,000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP > or = 160/90 mmHg. Forty-seven per cent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.

1. Regular aerobic exercise causes cardiovascular, neural, humoral and metabolic changes. Many of these are likely to influence cardiovascular risk and the changes vary according to the level and duration of increased physical activity. 2. The case for exercise exerting beneficial effects derives from epidemiological data showing that sedentary subjects have, on average, double the risk of cardiovascular disease of active individuals. Post-infarct rehabilitation studies are also consistent with a beneficial effect of exercise. Large randomized controlled intervention studies have not been performed. 3. These benefits may be due to the effects of regular exercise on risk factors, direct effects on atheromatous vessels, or improvement in survivability in established coronary heart disease by reducing arrythmias or increasing tolerance of ischaemia. 4. There are direct effects of regular exercise on blood pressure (BP) and lipid profiles. These occur at different levels of physical activity. Other changes which would be expected to reduce cardiovascular risk include increased insulin sensitivity, reduced sympathetic activity and increased gain of the baroreceptor-heart rate reflex and increased arterial compliance. 5. In hypertensives these changes may improve outcomes, irrespective of the reduction in BP reported in some randomized controlled intervention studies.

1. The effect of 4 weeks of moderate exercise training on cardiac left ventricular structure and function was examined by repeated echocardiographic/Doppler examination in 10 previously sedentary volunteers participating in a single blind, sedentary phase controlled, cross-over study. 2. Left ventricular internal diastolic diameter increased after 4 weeks of training from 4.98 to 5.11 cm with a further increase to 5.24 cm after 2 weeks of detraining (s.e.d. 0.05 cm, P < 0.01). These increases were still significant after adjustment for heart rate which fell from a pretraining average of 67.0-59.9 beats/min after 4 weeks of training. 3. There were no significant changes in systolic diameter or function and left ventricular wall thicknesses were unchanged during training, but were thinned after 2 weeks subsequent detraining. 4. The ratio of early to late transmitral filling velocity (E/A ratio) was significantly increased by training. Although E/A ratio was shown to be heart rate sensitive, training effects were still evident after adjustment for heart rate. 5. These changes in left ventricular volumes and function may contribute to the cardiovascular reflex changes previously shown to be produced by identical training programmes.

Changes in amplifying capacities of the hypertrophied heart and resistance vessels account for the characteristic evolution of haemodynamic patterns in the course of essential hypertension. Reversal of hypertrophy in established essential hypertension requires prolonged control of blood pressure. Redevelopment of hypertension on stopping drug therapy is slowest if there has been reversal of both vascular and cardiac hypertrophy. It may be possible to subsequently maintain normal blood pressure in a proportion of patients by non-pharmacological means following the initial period of drug therapy. Preliminary findings suggest that in a majority of patients the sympathetic nervous system may be overactive, whilst a smaller subset may have dysfunction of volume regulation.

1. In established chronic hypertension the amplifier properties of vessels and heart contribute about 70% to the maintenance of the elevated blood pressure (BP). Recent studies in spontaneously hypertensive rats (SHR) suggest that the structural changes occur very early and their amplifier properties may be critical for the development of hypertension. 2. In patients with primary hypertension, the greater the regression of cardiac and vascular hypertrophy, the slower the subsequent redevelopment of hypertension. Following regression of hypertrophy, the antihypertensive action of moderate regular exercise can maintain BP in the normal range in a proportion of patients. 3. Early treatment of SHR with enalapril greatly reduces the subsequent 'steady-state' BP in SHR. This produces virtually complete regression of vascular hypertrophy, but somewhat lesser degrees of regression of cardiac hypertrophy. 4. These studies serve as models for primary and secondary prevention of hypertension. A strategy based on intermittent drug and non-pharmacological therapy in man may contribute to the secondary prevention of atherosclerosis, in view of the adverse effects on lipid profiles of many antihypertensive drugs.